Methods and systems for heart failure prevention and treatments using ultrasound and leadless implantable devices

ABSTRACT

The present invention relies on a controller-transmitter device to deliver ultrasound energy into cardiac tissue in order to directly improve cardiac function and/or to energize one or more implanted receiver-stimulator devices that transduce the ultrasound energy to electrical energy to perform excitatory and/or non-excitatory treatments for heart failure. The acoustic energy can be applied as a single burst or as multiple bursts.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application claims the benefit of provisional U.S.application Ser. No. 60/713,241, filed Aug. 31, 2005, the fulldisclosure of which is incorporated herein by reference.

The disclosure of this application is also related to non-provisionalapplication Ser. No. 11/315,023, filed on Dec. 21, 2005, now U.S. Pat.No. 7,610,092, which claims priority to provisional application60/889,606 filed on Jun. 9, 2005, and to non-provisional applicationSer. No. 10/869,631, filed on Jun. 15, 2004, the full disclosures ofwhich are incorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The methods and systems of this invention relate to the prevention andtreatment of heart failure by means of a leadless external orimplantable device.

Heart Failure (HF) currently affects over 5 million patients in theUnited States alone. This population has been steadily increasing due tooverall demographic aging and, in particular, the effects of newlife-prolonging treatments to patients with chronic cardiac conditions.HF is defined by the ACC/AHA Task Force as a complex clinical syndromethat impairs the ability of the ventricle to fill with or eject blood.HF generally results from one or more underlying factors includinghypertension, diabetes, valvular disease, cardiomyopathy, coronaryartery disease, or structural changes to the heart muscle. HF ischaracterized by reduced ventricular wall motion in systole and/ordiastole, and low ejection fraction. As the heart becomes less able topump a sufficient volume of blood to the system, patients developsymptoms of fluid retention, shortness of breath, and fatigue. Patientswith cardiac disease or patients who experience cardiac problems, e.g.,ischemic episodes, are highly likely to eventually develop HF. It willbe beneficial to offer preventative treatment to these patients so thatthey might avoid or postpone becoming HF patients.

New medications developed to treat HF have been generally ineffective,and device-based solutions appear to offer significant promise forafflicted patients in both preventing heart failure initially andameliorating the progression of heart failure. The following aredescriptions of four device-based therapies to treat, prevent, and/ordelay progression of HF.

First, there are several reports of using therapeutic ultrasound toincrease cardiac contractility, reduce aortic pressure, cause coronaryvasodilatation, or increase tissue perfusion (tissue sonication). Thesereports describe the application of continuous and pulsed ultrasoundover a wide range of treatment durations, timing intervals, ultrasoundfrequencies, and ultrasound intensities. In isolated rat papillarymuscle, Forester et al. demonstrated increased contractility withcontinuous wave ultrasound. They speculated that the increase incontractility was due to the thermal effects or mechanical tensioneffects of ultrasound energy on the sarcolemma (external musclemembrane). Dalecki et al. found that the delivery of pulsed ultrasoundto the frog heart in systole resulted in a reduction in the peak aorticpressure. Miyamoto et al. reported vasodilation of coronary arteries incanine studies by short term ultrasound therapy, with the magnitude ofthe dilation similar to that of intracoronary nitroglycerin. Theyspeculated that the observed coronary vasodilation was a direct effecton vasomotor tone, and reported no temperature change to implicate athermal effect. Suchkova et al., applied ultrasound to the surface ofrabbit limb muscles following arterial ligation, and found that tissueperfusion was increased, accompanied by histologic evidence of dilatedcapillary beds. They further found this improvement in perfusion to beblocked by inhibition of nitric oxide synthase, implying that themechanism of effect was dependent upon nitric oxide. Finally, animalstudies have shown that ultrasound treatment can cause new myocardialtissue growth in conditions of chronic ischemia, and this is thought tobe due to up-regulation of growth factor expression.

Thus, a number of underlying mechanisms have been proposed to explainwhy therapeutic ultrasound may have beneficial effects on cardiacfunction. It is possible that increased myocardial contractility,reduced aortic pressure, coronary vasodilation, and increased tissueperfusion occur by separate or related mechanisms. For example, thevasodilation may be secondary to the increased myocardial demand causedby increased contractility. Alternatively, a reduction in aorticpressure (afterload) may result in increased contractility. Increasedtissue perfusion may be a manifestation of vasodilation at the capillarylevel.

While the exact mechanism(s) and sequence of events are not wellunderstood, the beneficial effects of therapeutic ultrasound on cardiacfunction can be utilized to improve the care of patients with heartfailure both chronically and during acute exacerbations. Long termimprovement in heart failure treatment is possible with chronicintermittent ultrasound administration. Coronary artery disease is theunderlying cause of HF in two-thirds of HF patients and coronary arterydisease can lead to acute ischemic episodes, which can be treated byimproving blood flow (reperfusion). Since ultrasound therapy can improveblood flow, therapeutic ultrasound can, thus, prevent HF. We havedescribed the use of ultrasound in co-pending application Ser. No.10/869,631, with methods and systems for leadless implantable devicesthat directly prevent and/or treat heart failure using ultrasoundenergy.

Second, the indications for permanent cardiac pacemaker implantationhave greatly expanded to include the treatment of heart failure bypacing both the left and right ventricle, called cardiacresynchronization therapy (CRT) or bi-ventricular pacing. Randomizedclinical trials have shown significant morbidity and mortality benefitswith bi-ventricular pacing, especially when combined with an implantablecardioverter defibrillator (ICD). As described in co-pending applicationSer. No. 11/315,023, and Ser. No. 11/315,524, a method of cardiacstimulation uses one or more implantable acoustic receiver-stimulatorsfor cardiac stimulation, along with an implanted or externally-appliedultrasound controller-transmitter. Using this leadless system to avoidlead limitations and complications and gain other potential advantagesas described in the co-pending applications, CRT therapy is applied tooptimal single or multiple sites in the left or right heart and mostnotably endocardial left ventricular sites.

Third, another device therapy applying electrical current to the heartmuscle is called Cardiac Contractility Modulation (CCM). These systemshave some similarities to conventional cardiac pacemakers, in that theycomprise a pulse generator implanted in the pectoral region of the chestand transvenous leads having electrodes in direct contact with hearttissue; in some cases, conventional pacemaker leads have been used inCCM therapy. However, in a conventional cardiac pacemaker, electricalcurrent is delivered at sufficient amplitude and duration at a time inthe cardiac cycle that will initiate a heart beat, known in the art asexcitation. In contrast, for CCM therapy, electrical current isdelivered during or immediately after a heart beat when the heart isunable to initiate another beat, known in the art as the absoluterefractory period of the heart. The amplitude and duration of theelectrical current would be sufficient for excitation, but since it isdelivered in this refractory period it is thus considerednon-excitatory. Instead of initiating a heat beat via excitation, theelectrical field or electrical current delivered for CCM increasestissue contractility during the heart beat. As noted earlier, increasedtissue contractility leads to improved cardiac function. It has beenshown in basic investigational studies using this CCM approach that theaction potential duration is prolonged during this non-excitatoryelectrical field delivery. It is thought that the underlying mechanismis an increase in calcium transport into the cells.

Early animal studies (Mohri et al.) employed two pairs of electrodes,one pair in the anterior LV wall and one pair in the posterior wall;each with approximately 3 cm inter-electrode distance. CCMnon-excitatory electrical field delivery (20 mA biphasic square-waves of30 ms duration) was delivered 30 ms after local R wave detection,between each electrode pair. An increase in contractility was found witheither anterior or posterior delivery, but was greatest withsimultaneous delivery to both the anterior and posterior pairs. Theincrease in contractility only occurred in the regions of electricalcurrent delivery.

In acute human studies (Pappone et al.), CCM therapy was deliveredeither across two selected poles of an octapolar catheter in thecoronary sinus (CS), on the epicardial aspect of the LV or on the RVseptum from the tip electrode to the ring electrode of a commerciallyavailable active fixation pacing lead. The CCM current used was abiphasic, square-wave pulse 20-40 ms in duration, delivered 30-60 msafter detection of an electrical pulse using the local electrogram, withpulse amplitudes up to 14 mA. With LV delivery of 10 mA to the CS, somepatients complained of chest discomfort. With RV septum delivery, 14 mAwas able to be delivered without chest discomfort. Acute improvement inLV function was similar with LV or RV delivery; approximately a 9%increase in pressure gradient dP/dt_(max) and 10% increase in aorticpulse pressure.

One example of a CCM device is an Optimizer™ II (Impulse Dynamics,Israel). These have been implanted in patients and have been shown toimprove cardiac function (Pappone et al., Stix et al.). This deviceemploys one commercially available right atrial lead used for sensingonly, and 2 commercially available transvenous bipolar active fixationleads implanted in the RV septum used for sensing a local electrogramand delivery of non-excitatory electrical current.

Because CCM devices use leads similar to cardiac pacemakers, they aresubject to all the limitations and complications associated withcurrently available cardiac pacemakers. These lead issues have beenextensively identified in our co-pending applications listed above.Additionally, although animal studies had shown greater efficacy withplacement of the electrodes on the left ventricle, in clinical studiesusing coronary sinus leads for left ventricular non-excitatory CCMtherapy, patients experienced chest pain, attributed to stimulation ofthe phrenic nerve. In the same patients, endocardial delivery to theright ventricular septum did not cause discomfort. It is likely, basedon animal study results, that CCM therapy would be substantiallyimproved using a system that enables endocardial left ventricularnon-excitatory therapy.

Therefore, it would be desirable to provide a system without the needfor transvenous leads, with the ability to optimally select sites on theendocardium, particularly in the left ventricle, and to select multiplesites for CCM delivery of non-excitatory electrical current.

Fourth, the concept of selective site pacing to initiate a preferredpattern of cardiac activation and/or mechanical contraction has beenrecently put forth to prevent heart failure in patients needingpermanent pacing for bradycardia indications. Traditionally, thestandard ventricular site for stimulation has been the RV apex forreasons of lead stability and ease of implantation. However, recentrandomized clinical trials of patients requiring bradycardia pacing(DAVID and PAVE) have lead to the conclusion that the RV apex locationis deleterious. The concept of selective site pacing has emerged, andhas led to the reevaluation of all traditional pacing sites. Newstimulation sites being evaluated require the use of non-passivefixation tips and more precise implant techniques. The ideal site(s) maybe within the left ventricle in areas inaccessible using transvenousleads from within the coronary sinus. Selective site left ventricular orright ventricular stimulation alone may provide improved heartfunctioning or prevention of heart failure without the need forbi-ventricular stimulation. It would be desirable to provide selectivesite pacing with previously referred to leadless methods and systemsusing one or more implantable acoustic receiver-stimulators for cardiacstimulation, along with an implanted or externally-applied ultrasoundcontroller-transmitter. The receiver-stimulator would be implanted inthe left and/or right ventricle at one or more locations that initiate apreferred pattern of cardiac activation and/or mechanical contraction.

It would be desirable to treat patients who have had cardiac problems toprevent or delay them from becoming HF patients. It would be ideal toprovide a single system to take advantage of the benefits ofsonification, pacing and CCM and either based on user preference,pre-programmed therapy, or physiologic parameters that are measured,individual or combination treatments (sonication, pacing or CCM) couldbe provided.

Thus, it would further be desirable to provide an implantable devicethat combines the beneficial effects of direct application of ultrasoundenergy to cardiac tissue with the beneficial effects of a leadlesselectrical delivery device for cardiac resynchronization stimulationtherapy, cardiac contractility modulation therapy, and/or selective sitepacing therapy in order to improve cardiac function in heart failurepatients or to prevent heart failure in other patients.

2. Description of the Background Art

-   U.S. Pat. No. 4,651,716 Forester; George V. et al. Method and device    for enhancement of cardiac contractility.-   U.S. Pat. No. 6,522,926 Kieval, et al.; Devices and methods for    cardiovascular reflex control.-   U.S. Pat. No. 3,659,615, Enger; Encapsulated Non-Permeable    Piezoelectric Powered Pacesetter, May 1972-   U.S. Pat. No. 4,256,115, Bilitch; Leadless Cardiac Pacer, March 1981-   U.S. Pat. No. 4,690,144, Rise et al; Wireless Transcutaneous    Electrical Tissue Stimulator, September 1987-   U.S. Pat. No. 5,170,784, Ramon et al; Leadless Magnetic Cardiac    Pacemaker, December 1992-   German Patent DE4330680 (abandoned), Zwicker; Device for Electrical    Stimulation of Cells within a Living Human or Animal, March 1995-   U.S. Pat. No. 5,405,367, Schulman et al; Structure and Method of    Manufacture of an Implantable Microstimulator, April 1995-   U.S. Pat. No. 5,411,535, Fujii et al; Cardiac Pacemaker Using    Wireless Transmission, May 1995-   U.S. Pat. No. 5,749,909, Schroeppel et al; Transcutaneous Energy    Coupling Using Piezoelectric Device, May 1998-   U.S. Pat. No. 5,751,539, Stevenson et al; EMI Filter for Human    Implantable Heart Defibrillators and Pacemakers, May 1998-   U.S. Pat. No. 5,766,227, Nappholz et al; EMI Detection in an    Implantable Pacemaker and the like, May 1998-   U.S. Pat. No. 5,814,089, Stokes et al; Leadless Multisite    Implantable Stimulus and Diagnostic System, September 1998-   U.S. Pat. No. 5,817,130, Cox et al; Implantable Cardiac    Cardioverter/Defibrillator with EMI Suppression Filter with    Independent Ground Connection, October 1998-   U.S. Pat. No. 5,978,204, Stevenson; Capacitor with Dual Element    Electrode Plates, November 1999-   U.S. Pat. No. 6,037,704, Welle; Ultrasonic Power Communication    System, March 2000-   U.S. Pat. No. 6,366,816, Marchesi; Electronic Stimulation Equipment    with Wireless Satellite Units, April 2002-   U.S. Patent Application Publication 2002/0077673, Penner et al;    Systems and Methods for Communicating with Implantable Devices, June    2002-   U.S. Pat. No. 6,424,234, Stevenson; Electromagnetic Interference    (EMI) Filter and Process for Providing Electromagnetic Compatibility    of an Electronic Device while in the Presence of an Electromagnetic    Emitter Operating at the Same Frequency, July 2002-   U.S. Pat. No. 6,445,953, Bulkes et al; Wireless Cardiac Pacing    System with Vascular Electrode-Stents, September 2002-   U.S. Pat. No. 6,654,638, Sweeney; Ultrasonically Activated    Electrodes, November 2003-   U.S. Patent Application Publication 2004/0172083, Penner;    Acoustically Powered Implantable Stimulating Device, September 2004-   WO9725098, Shlomo et al; Electrical Muscle Controller, July 1997-   U.S. Pat. No. 6,725,093, Ben-Haim et al; Regulation of excitable    tissue control of the heart based on physiological input, April 2004-   U.S. Pat. No. 6,463,324, Ben-Haim et al; Cardiac output enhanced    pacemaker, October 2002-   U.S. Pat. No. 6,442,424, Ben-Haim et al. Local cardiac motion    control using applied electrical signals, August 2002-   U.S. Pat. No. 6,363,279, Ben-Haim et al; Electrical muscle    controller, March 2002-   U.S. Pat. No. 6,330,476, Ben-Haim et al; Electrical muscle    controller using a non-excitatory electric field, December 2001-   U.S. Pat. No. 6,317,631, Ben-Haim et al; Controlling heart    performance using a non-excitatory electric field, November 2001-   U.S. Pat. No. 6,298,268, Ben-Haim et al; Cardiac output controller,    October 2001-   U.S. Pat. No. 6,285,906, Ben-Haim et al; Muscle contraction assist    device, September 2001-   U.S. Pat. No. 6,236,887, Ben-Haim et al; Drug-device combination for    controlling the contractility of muscles, May 2001-   U.S. Pat. No. 6,233,484, Ben-Haim et al; Apparatus and method for    controlling the contractility of muscles, May 2001-   ACC/AHA Task Force on Practice Guidelines. Evaluation and Management    of Chronic Heart Failure in the Adult. JACC 2002; 38:2101-13.-   Miyamoto T et al. Coronary Vasodilation by Noninvasive    Transcutaneous Ultrasound An In Vivo Canine Study. Journal of the    American College of Cardiology. 2003; 41:1623-7.-   McPherson D and Holland C. Seizing the Science of Ultrasound Beyond    Imaging and Into Physiology and Therapeutics. Journal of the    American College of Cardiology 2003; 41:1628-30.-   Forester G V, Roy O Z, and Mortimer A J. Enhancement of    contractility in rat isolated papillary muscle with therapeutic    ultrasound. Mol. Cell Cardiol. 1982; 14(8):475-7.-   Suchkova V N, et al. Ultrasound improves tissue perfusion in    ischemic tissue through a nitric oxide-dependent mechanism. Throm    Haemost. 2002; 88:865-70.-   Dalecki D. et al. Effects of pulsed ultrasound on the frog heart: I.    Thresholds for changes in cardiac rhythm and aortic pressure.    Ultrasound in Med & Biol. 1993; 19:385-390.-   Mortimer A J et al. Letter to the Editor: Altered Myocardial    Contractility with Pulsed Ultrasound. Ultrasound in Med and Biol.    1987; 13(9):L567-9-   Forester G V et al. Ultrasound Intensity and Contractile    Characteristics of Rat Isolated Papillary Muscle. Ultrasound in Med.    And Biol. 1985; 11(4):591-598.-   Meltzer R S, Schwarz K Q, et al. Therapeutic Cardiac Ultrasound.    American Journal of Cardiology. 1991; 67:422-4-   Kass D A, Chen C-H, Curry C, Talbot M, Berger R, Fetics B, Nevo E.    Improved Left Ventricular Mechanics from Acute VDD Pacing in    Patients with Dilated Cardiomyopathy and Ventricular Conduction    Delay. Circulation 1999; 99:1567-73.-   Abraham W T, Fisher W G, Smith A L, Delurgio D B, Leon A R, Loh E,    Kocovic D Z, Packer M, Clavell A L, Hayes D L, Ellestad M, Messenger    J, for the MIRACLE study group. Cardiac Resynchronization in Chronic    Heart Failure. N Engl J Med, 2002; 346:1845-53.-   Nishida T, et al. Extracorporeal cardiac shock wave therapy markedly    ameliorates ischemia-induced myocardial dysfunction in pigs in vivo.    Circulation. 2004; 110:3055-3061.-   Mohri S, et al. Cardiac contractility modulation by electric    currents applied during the refractory period. Am J Physiol Heart    Circ Physiol. 2002; 282:H1642-1647.-   Marrouche N F et al. Nonexcitatory stimulus delivery improves left    ventricular function in hearts with left bundle branch block. J    Cardiovasc Electrophysiol. 2002; 13:691-695.-   Mond H G, Gammage M D. Selective Site Pacing: The Future of Cardiac    Pacing? PACE 2004; 27:835-836.-   Peschar M, et al. Left ventricular septal and apex pacing for    optimal pump function in canine hearts. J Am Coll Cardiol 2003;    41:1218-1226.-   DAVID Trial Investigators. The Dual Chamber and VVI Implantable    Defibrillator (DAVID) Trial. JAMA 2002; 288:3115-3123.-   Doshi, R N, et al. The Left Ventricular-Based Cardiac Stimulation    Post AV Nodal Ablation Evaluation (PAVE) Study, oral presentation at    American College of Cardiology, March 2004.-   Pappone C, et al. Cardiac Contractility Modulation by electric    currents applied during the refractory period in patients with heart    failure secondary to ischemic or idiopathic dilated cardiomyopathy.    Am J Cardiol 2002; 90:1307-1313.-   Pappone C, et al. First human chronic experience with cardiac    contractility modulation by nonexcitatory electrical currents for    treating systolic heart failure: mid-term safety and efficacy    results from a multicenter study. J Cardiovasc Electrophysiol 2004;    15:418-427.-   Stix G, et al. Chronic electrical stimulation during the absolute    refractory period of the myocardium improves severe heart failure.    European Heart J 2004; 25:650-655.

BRIEF SUMMARY OF THE INVENTION

The devices of the present invention deliver ultrasound energy to theheart and/or deliver ultrasound energy to receiver-stimulator devices.Delivered at therapeutic levels, the ultrasound energy directly improvescardiac function by increasing contractility, vasodilation, and tissueperfusion, etc. This leads to prevention of HF in patients who arelikely to become HF patients, if left untreated, and in patents who arealready diagnosed with HF. Delivered at sufficient amplitudes, theultrasound energy is transduced into electrical energy by implantedreceiver-stimulator devices that have been implanted in the hearttissue, providing either excitatory or non-excitatory energy deliveryfor the treatment of heart failure. In combination, ultrasound therapyand receiver-stimulator device therapy provide multiple benefits asheart failure therapies, including preventing patients from degeneratinginto HF. The use of ultrasound as the single energy source providesefficient selection of individual and combined therapies, as well astissues sites, for delivering the therapy.

The present invention relies on acoustic energy delivery using anexternal or implantable device to provide beneficial effects forpatients with heart failure including 1) the ability to improve cardiacfunction from the exposure of acoustic energy to cardiac tissue, and/or2) the ability to transmit acoustic energy to implanted receivers toprovide excitatory and non-excitatory stimulation, in patients sufferingfrom or at risk of heart failure.

We have previously disclosed methods and systems to treat heart failureby means of a leadless implantable device delivering vibrational(ultrasound, acoustic) energy from a controller-transmitter device todirectly improve cardiac function. We have also previously disclosedmethods and devices of leadless implantable systems for the electricalstimulation of cardiac tissue using ultrasound as a means to transmitenergy and signal information from a controller-transmitter devicethroughout the body to one or more receiver-stimulator devicescontaining means to receive such ultrasound, convert it into electricalenergy, and then apply that electrical energy to stimulating electrodesas cardiac resynchronization therapy for the treatment of heart failure.See co-pending application Ser. No. 11/315,023, filed Dec. 21, 2005;Ser. No. 11/315,524, filed Dec. 21, 2005; and patent application Ser.No. 10/869,631, filed Jun. 15, 2004, the full disclosures of which areincorporated here by reference.

In all these co-pending applications, acoustic energy is applied from anexternal or implanted controller-transmitter to the heart tissue toprovide at least one of an increase in contractility, vasodilation,tissue perfusion, and/or an increase in cardiac output for the treatmentof heart failure.

In some of these co-pending applications, acoustic energy is appliedfrom an external or implanted controller-transmitter to implantedreceiver-stimulator devices in the heart to provide electrical deliveryfor bi-ventricular pacing or selective site pacing.

It is an intent of this invention to provide methods and systems for theleadless electrical delivery of non-excitatory therapy in cardiaccontractility modulation for the treatment of heart failure. It is afurther intent of this invention to provide methods and systems for theleadless electrical delivery of excitatory therapy for the prevention ofheart failure. It is still a further intent of this invention to providemethods and systems to select and deliver separate heart failuretreatment and preventive therapies within a single system. It is yetanother intent of this invention to provide methods and systems tocombine and deliver in a single system multiple heart failure treatmentand preventive therapies to yield multiple therapeutic benefits.

External or implanted controller-transmitters according to the presentinvention are configured to apply acoustic energy to at least a portionof the heart, usually including at least a ventricular region(s) of theheart and typically including regions of the heart with implantedreceiver-stimulator devices.

A controller-transmitter device may be implanted utilizing knownsurgical techniques subcutaneously, above or beneath the pectoralmuscles, near the heart. This device will typically contain some, most,or all elements of currently available pacemaker systems, with specificadaptations pertinent to this invention. Such typical elements mayinclude a power source, such as a battery or a rechargeable battery;logic control and timing circuitry; a sensing system, typicallycomprising sensing electrodes, motion detectors, and other types ofphysiologic sensors; signal conditioning and analysis functions for thevarious electrodes and detectors; and a system to communicate with anoutside console for data transmission, diagnostic, and programmingfunctions typically through a radiofrequency (RF) link. Additionally,the controller-transmitter device usually contains an ultrasoundamplifier and an ultrasound transducer to generate acoustic energy, andto transmit such energy in the general direction of the heart andspecifically in the direction of the implanted receiver-stimulatordevice. Beam profiles of the transmitted acoustic energy may be adaptedto target portions of the heart or implanted receiver-stimulatordevices. The duration, timing, and power of the acoustic energytransmission would be controlled as required, in response to detectednatural or induced physiological events or conditions, and perprogrammed parameters of the device, by the logic control electronics.

In order to provide excitatory or non-excitatory electrical delivery tocardiac tissue employing ultrasonic energy transfer, the presentinvention comprises an implantable receiver-stimulator device adapted tobe implanted at or attached to the desired location eitherendocardially, epicardially, or intramyocardially. Various techniquesand tools (catheters, stylets) that are commonly known could be used toimplant the receiver-stimulator device at these locations. Thereceiver-stimulator would be adapted to provide permanent attachment atthe implant site including possibly helical coils, barbs, tines, clips,or the like, or by bonding onto its outer surface materials which areknown to stimulate cellular growth and adhesion. Alternatively, thereceiver-stimulator could be adapted for implantation in the coronaryvasculature at preferred sites for stimulation, e.g., being incorporatedinto a stent-like platform suitable for intravascular delivery anddeployment. Functionally, the receiver-stimulator device comprises 1) anultrasound transducer to receive the acoustic energy transmitted from acontroller-transmitter device and transform it into electrical energy,2) an electrical circuit to transform the alternating electrical energyinto a direct current or a waveform having other characteristics (e.g.,multiphase waveforms), and 3) electrodes to transfer the electricalenergy to the myocardium.

A single receiver-stimulator device may be implanted as described abovefor single site excitatory or non-excitatory electrical delivery tocardiac tissue. Alternatively, a plurality of receiver-stimulatordevices could be implanted to deliver excitatory or non-excitatoryelectrical energy to cardiac tissue, either by simultaneous, sequentialor independent activation of the receiver-stimulator devices. Thetransmitted acoustic energy can activate the stimulators simultaneouslyor sequentially through fixed or programmable delays after receiving thesame transmitted acoustic energy, or independently by responding only toacoustic energy of a specific character (i.e., of a certain frequency,amplitude, or by other modulation or encoding of the acoustic waveform)intended to energize only that specific device.

In one embodiment, a controller-transmitter would contain programmableparameter settings to activate receiver-stimulators that have beenimplanted at critical sites to deliver leadless non-excitatory CCMtherapy to improve cardiac function of heart failure patients. Aplurality of receiver-transmitters would be implanted into the leftand/or right heart at selected locations in order to provide anon-excitatory electrical field. The controller-transmitter wouldinclude sensing electrodes on, connected to, or incorporated into itsexternal surface and signal processing circuitry and algorithms to allowit to detect the patient's electrogram (electrocardiographic recording).Signal processing and specialized algorithms would recognize intrinsicatrial and/or ventricular activation and possibly alsoelectrocardiographic indices of action potential duration such as the QTinterval. Following a detected intrinsic ventricular activation and aprogrammed delay interval, the controller-transmitter would thenactivate the receiver-stimulator devices at energy levels that aretherapeutic.

In another embodiment, a controller-transmitter would containprogrammable parameters to activate receiver-stimulators that have beenimplanted at critical sites to deliver excitatory (pacing) therapy toprevent heart failure.

In yet another embodiment, a controller-transmitter would containprogrammable parameter settings to provide direct therapeutic sonicationof ventricular tissue, and contain programmable parameters to activatereceiver-stimulators to deliver leadless bi-ventricular pacing therapyor site selected pacing therapy for heart failure, and containprogrammable parameters to activate receiver-stimulators that have beenimplanted at critical sites to deliver pacing therapy as a prevention ofheart failure, and contain programmable parameters to activatereceiver-stimulators that have been adapted and implanted in criticalsites to deliver CCM therapy to improve the tissue condition of heartfailure patients.

In another preferred embodiment, a controller-transmitter would containprogrammable parameters settings to deliver combinations of therapy fordirect therapeutic sonication of ventricular tissue, leadlessbi-ventricular or critical site pacing, heart failure prevention pacing,and/or CCM therapy. In such an embodiment one or morereceiver-stimulator elements adapted for its specific function wouldnecessarily be implanted at desired locations within the heart,preferably fully embedded within the myocardium. The specializedcontroller-transmitter would then be implanted subcutaneously at alocation allowing sonication of tissue in both ventricles and activationof one or more implanted receiver-stimulators. Any of the therapiesdescribed could be used independently or in combination to accomplishmulti-beneficial therapy. The controller-transmitter would includesensing electrodes on or incorporated into its external surface andsignal processing circuitry and algorithms to allow it to detectphysiologic parameters (e.g. electrograms, pacing artifact signals froman implanted conventional pacemaker, pressure, heart sounds,motion/activity, etc.) to allow algorithmic adjustment to one or moretherapies.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of the components of a system constructedaccording to the principles of the present invention.

FIG. 2 illustrates a controller-transmitter implanted over a patient'sheart and in communication with a receiver-stimulator and an externalprogrammer.

FIG. 3 a illustrates prior art timing parameters.

FIG. 3 b illustrates a system for performing CCM therapy directly oncardiac tissue.

FIGS. 4 a-4 d illustrate different implantation sites for thereceiver-stimulator.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relies on a controller-transmitter device todeliver ultrasound energy to cardiac tissue to directly improve cardiacfunction and/or to energize one or more implanted receiver-stimulatordevices that transduce the ultrasound energy to electrical energy toperform excitatory and/or non-excitatory treatments for heart failure.The acoustic energy can be applied as a single burst or as multiplebursts with appropriate selection of the following parameters:

Parameter Value Range Ultrasound frequency 20 kHz-5 MHz Ultrasound BurstDuration 0.1 μS-100 mS Duty Cycle 0.001-6.0% Mechanical Index ≦1.9

FIG. 1 is a block diagram of the present invention. An implantablecontroller-transmitter device 1 contains an ultrasound transducer 16 (ormultiple transducers) of appropriate size(s) and aperture(s) to generatesufficient acoustic power to achieve the desired heart failure therapy.The transducer(s) 16 within the controller-transmitter device 1 areconstructed of specific designs, including aperture size, acousticfrequency, materials, and arrangement to provide the appropriate beamcharacteristics for individual embodiments, implant sites, and patientcharacteristics. The controller-transmitter 1 contains the power source,typically a battery 10, ultrasound amplifier 15, transmission powerconditioning 17, control and timing electronics and logic 14,physiologic sensor interface electronics 12, sensors 11 eitherencapsulated in the device or connected to the device, and acommunication module 13 typically an RF communication interface to anexternal control and programming device 3. An externalcontroller-transmitter would contain the same elements, except theexternal programmer 3 and RF communication module 13. The externalcontroller-transmitter would have an operator-controlled interface (notshown) to adjust device parameters.

The transducer(s) 16 may comprise a single element or several elementsin a linear, two-dimensional, or segmented array (not shown). In thecase of an array, each element may have its own amplifier 15 and controland timing electronics and logic 14 such that the acoustic beam might befocused or diffused depending on the desired function or effect, orsteered to a desired location, or that the beam may be swept to coverseveral sites in sequential order, or any combination thereof.

The one or more receiver-stimulator implants 2 contain a receivertransducer 18, circuitry 19 to detect, impedance match, and convert thereceived ultrasound energy into an electrical output, and electrodes 20.Multiple receiver-stimulator devices 2 may function simultaneously; itis also possible for multiple devices to function sequentially byincorporating different delays within the circuitry 19, orindependently, either by responding only to a specific transmittedfrequency by steering the transmit beam to specific devices, or throughthe use of a selective modulation technique such as amplitudemodulation, frequency modulation, pulse width modulation, or throughencoding techniques including time-division multiplexing, which would bediscriminated by adapting circuitry 19.

FIG. 2 illustrates the functional components of the present inventionfor an implanted embodiment. The controller-transmitter device 1containing the transmitting transducer would be implanted typically justbeneath the skin in the subcutaneous space but could also be placedbeneath the pectoral muscles. In particular, it is desirable to be ableto direct the ultrasonic energy over the left ventricle in order toassure maximum effectiveness. As the heart is located beneath the ribsand sternum, the controller-transmitter device 1 must be properlylocated to deliver the energy. At frequencies lower than 1 MHz, acousticattenuation due to bone and cartilage is less problematic.

The receiver-stimulator device(s) 2 would be implanted typically usingan endocardial placement technique by an active fixation mechanism suchas a helical screw-in element. Alternatively the receiver-stimulatordevice(s) 2 could be implanted using a minimally invasive surgicalapproach to the epicardial aspects of the heart or deliveredtransvascularly into, for example, the coronary sinus. Locations for thereceiver-stimulator devices would be chosen to optimize the desiredelectrical therapy.

The controller-transmitter device 1 would typically includephysiological sensors 11 (not shown) such as electrodes disposed on theouter surface of the device, for detecting the patient's electrogram,and in certain embodiments additional physiological sensors includingbut not limited to sensors which would detect the patient's motion,blood pressure, respiration, and/or heart sounds. Circuitry andalgorithm logic 14 for utilizing these signals for control of thedevices' therapeutic function could be incorporated in the system. Suchelectrodes and other sensors would be preferably disposed on orincorporated into or within the housing of the controller-transmitterdevice.

An external programmer 3 is used to program device parameters in thecontroller-transmitter 1, typically using an RF telemetry link.Programming of the controller-transmitter includes the selection of oneor more of the following types of therapies: (i) Sonication of hearttissue to improve cardiac function; (ii) Site-selected pacing forprevention of heart failure; (iii) Multi-site pacing (e.g.bi-ventricular pacing) for treatment of heart failure; and (iv) CardiacContractility Modulation to improve contractility.

Alternatively, the acoustic transmitter function for direct therapeuticsonication of heart tissue might also be incorporated within a devicedelivering conventional lead-based electrical current (not shown), forexample, within a CRT device or within a CCM device wherein theconventional lead/electrode system would provide sensing from andelectrical delivery to cardiac tissue and the acoustic transmissionwould provide ultrasound therapy for heart failure.

FIG. 3 a, shown adapted from prior art (Mohri), is an example toillustrate the types of timing needed within for the control circuitry14 to perform CCM therapy using the present invention. Sensingelectrodes on a controller-transmitter device 1 provide a signal similarto the surface ECG shown in the diagram. The onset of electricalventricular activation is detected, and after a specified delay (hereshown as 30 msec), the transmitter delivers acoustic energy for aspecified duration which is transduced by circuitry 19 into anappropriate electrical waveform. The duration of the electrical delivery(here shown as 30 msec) is equal to the duration of acoustic delivery.In this example, the electrical waveform is biphasic (positive squarewave followed by negative square wave) with an amplitude of 20 mA, butother waveforms may be used.

FIG. 3 b shows a preferred embodiment for a system combining directacoustic therapy to the cardiac tissue with CCM therapy. In FIG. 3 b,two receiver-stimulator devices 2 are implanted into the rightventricle, one in the septum and the other at the apex. Other implantlocations in the right and left ventricle may be selected for any numberof receiver-stimulators 2. Inherent ventricular activation is detectedfrom sensing electrodes incorporated on the controller-transmitter 1whereby the control circuitry properly times the initiation of thedelivery of acoustic energy to the two implanted receiver-stimulators 2to initiate non-excitatory therapy.

FIGS. 4 a-4 d depict various illustrations of receiver-stimulatorimplant site selections. FIG. 4 a is a cross-sectional view of the heartshowing a single receiver-stimulator device 2 implanted into the leftventricular myocardium. Such an embodiment may be functional for sitespecific pacing for the prevention of heart failure in a patient needingbradycardia pacing support, for site specific pacing for the treatmentof heart failure, or for CCM therapy to improve cardiac contractility ina heart failure patient. As shown, with appropriate placement of thecontroller-transmitter 1, both the cardiac tissue and thereceiver-stimulator 2 will receive ultrasound waves thus providing anopportunity for sonication therapy in a heart failure patient.

FIG. 4 b is a cross-sectional view of the heart showing a singlereceiver-stimulator 2 implanted into the ventricular septum, receivingacoustic energy from controller-transmitter 1. Similarly, such anembodiment may be functional for site specific pacing for the preventionof heart failure in a patient needing bradycardia pacing support or forCCM therapy delivery to improve the wall motion characteristics of theseptum in a patient with HF.

FIG. 4 c shows a further adaptation wherein two receiver-stimulatordevices 2 are implanted to achieve a completely leadless multi-sitepacemaker configuration for example as in bi-ventricular pacing or amulti-site CCM therapy delivery for HF treatment. The firstreceiver-stimulator 2 is shown attached to the right ventricular apexwith the second being attached to the left ventricular free wall. Bothreceiver-stimulator devices 2 and the ventricles receive acoustic energyfrom controller-transmitter 1 simultaneously. Direct beneficialsonication therapy may be delivered to the ventricles. Excitatory(pacing) and non-excitatory (CCM) therapy may be delivered eithersimultaneously or selectively.

FIG. 4 d shows another alternative embodiment. In this example, fourreceiver-stimulator devices 2 are implanted into the right and leftventricle and can be used for multiple therapy concepts. As in FIG. 4 c,since the ultrasound is delivered to the cardiac tissue andreceiver-stimulators simultaneously, direct beneficial sonicationtherapy may be delivered simultaneously. Excitatory (pacing) andnon-excitatory (CCM) therapy may be delivered either simultaneously orselectively.

Optionally, but not shown, a receiver-stimulator 2 could also beimplanted into the atrial tissues of the heart. Optionally, but notshown, this multi-therapy concept could integrate the ultrasoundsonication therapy with a conventional dual chamber pacemaker (DDD),dual chamber ICD, bi-ventricular pacemaker (CRT-P), biventricularpacemaker ICD (CRT-D), or a CCM therapy device.

Optionally, the invention can provide three types of heart failuretreatments to the patient either separately or in combination; directsonication of the ventricular tissue, cardiac contractility modulationtherapy, and excitatory pacing stimulation.

1. A system for the delivery of electrical current to a patient's heartto improve and/or prevent deterioration of heart function, comprising:one or more acoustic receiver-stimulators having an electrode assemblywherein at least one of the electrodes is adapted to be implanted indirect contact with cardiac tissue; and an acousticcontroller-transmitter, wherein the acoustic controller-transmitter isadapted to transmit acoustic energy into a patient's body and whichprovides both energy and signal information to the receiver-stimulatorand the receiver-stimulator further comprises an acoustic receiver whichreceives the acoustic energy and generates alternating current, meansfor converting the alternating current to a direct current or waveformto provide a non-excitatory electrical current to the electrodes adaptedto deliver the direct current or waveform to the cardiac tissue, whereinthe implantable receiver-stimulator is adapted to be placed and securedat a location in the heart sufficient to deliver electrical energy tothe cardiac tissue and wherein the controller-transmitter is adapted totransmit acoustic energy such that the receiver-stimulator deliversnon-excitatory electrical current which prolongs action potentialduration.
 2. A system as in claim 1, wherein the non-excitatoryelectrical current further improves tissue contractility.
 3. A system asin claim 1, wherein the one or more implantable receiver-stimulators areadapted to be placed and secured at one or more ventricular locations.4. A system as in claim 3, wherein the one or more implantablereceiver-stimulators are adapted to be placed and secured in the rightventricle.
 5. A system as in claim 3, wherein the one or moreimplantable receiver-stimulators are adapted to be placed and secured inthe left ventricle.
 6. A system as in claim 1, wherein the acousticenergy is transmitted during an absolute refractory period.
 7. A systemas in claim 1, wherein the acoustic energy is transmitted at the time ofor delayed from a detected physiologic event.
 8. A system as in claim 1,wherein the acoustic energy is transmitted on command from an externalcommunication source.
 9. A system as in claim 1, wherein thecontroller-transmitter is applied externally on the patient's body. 10.A system as in claim 1, wherein the controller-transmitter isimplantable in the patient's body in a subcutaneous region and directsacoustic energy to the receiver-stimulator.
 11. A method for treating apatient suffering from heart failure (HF) by prolonging action potentialduration in cardiac tissue, said method comprising: transmitting from acontroller-transmitter an acoustic signal in a patient's body to areceiver-stimulator implanted in a patient's heart, receiving theacoustic signal using the implantable receiver stimulator, wherein thereceiver-stimulator generates an alternating current in response to theacoustic signal and converts the alternating current to a direct currentand/or waveform to stimulate cardiac tissue, delivering the directcurrent to cardiac tissue, wherein the acoustic signal provides bothenergy and signal information to deliver non-excitatory electricalcurrent to cardiac tissue.
 12. A method as in claim 11, wherein thedirect current is delivered to the cardiac tissue by electrodes disposedon the receiver-stimulator.
 13. A method as in claim 12, wherein thereceiver stimulators are implanted in the left and/or right ventricles.14. A method as in any one of claims 11, 12 and 13, wherein the directcurrent is converted to non-excitatory current which improves tissuecontractility.
 15. A method as in claim 14, wherein the non-excitatorycurrent is delivered during an absolute refractory period.
 16. A methodas in claim 14, wherein the non-excitatory current is delivered at atime of or delayed from a detected physiologic event.
 17. A method as inclaim 14, wherein the non-excitatory current is delivered on commandfrom an external communication source.
 18. A method as in claim 11,wherein the controller-transmitter is applied externally on thepatient's body.
 19. A method as in claim 11, wherein thecontroller-transmitter is implantable in the patient's body in asubcutaneous region that directs acoustic energy to the heart.
 20. Amethod as in claim 11, wherein the patient has been diagnosed assuffering from heart failure (HF).